A novel, effective machine learning-based RNA editing profile for predicting the prognosis of lower-grade gliomas

Patients with low-grade glioma (LGG) may survive for long time periods, but their tumors often progress to higher-grade lesions. Currently, no cure for LGG is available. A-to-I RNA editing accounts for nearly 90% of all RNA editing events in humans and plays a role in tumorigenesis in various cancers. However, little is known regarding its prognostic role in LGG. On the basis of The Cancer Genome Atlas (TCGA) data, we used LASSO and univariate Cox regression to construct an RNA editing site signature. The results derived from the TCGA dataset were further validated with Gene Expression Omnibus (GEO) and Chinese Glioma Genome Atlas (CGGA) datasets. Five machine learning algorithms (Decision Trees C5.0, XGboost, GBDT, Lightgbm, and Catboost) were used to confirm the prognosis associated with the RNA editing site signature. Finally, we explored immune function, immunotherapy, and potential therapeutic agents in the high- and low-risk groups by using multiple biological prediction websites. A total of 22,739 RNA editing sites were identified, and a signature model consisting of four RNA editing sites (PRKCSH|chr19:11561032, DSEL|chr18:65174489, UGGT1|chr2:128952084, and SOD2|chr6:160101723) was established. Cox regression analysis indicated that the RNA editing signature was an independent prognostic factor, according to the ROC curve (AUC = 0.823), and the nomogram model had good predictive power (C-index = 0.824). In addition, the predictive ability of the RNA editing signature was confirmed with the machine learning model. The sensitivity of PCI-34051 and Elephantin was significantly higher in the high-risk group than the low-risk group, thus potentially providing a marker to predict the effects of lung cancer drug treatment. RNA editing may serve as a novel survival prediction tool, thus offering hope for developing editing-based therapeutic strategies to combat LGG progression. In addition, this tool may help optimize survival risk assessment and individualized care for patients with low-grade gliomas.